INVESTIGADORES
SARAVIA Flavia Eugenia
artículos
Título:
Reduced hippocampal neurogenesis and number of hilar neurons in streptozotocin-induced diabetic mice: reversion by antidepressant treatment.
Autor/es:
BEAUQUIS, J.; ROIG, P.; HOMO-DELARCHE, F.; DE NICOLA, AF; SARAVIA, F.
Revista:
EUROPEAN JOURNAL OF NEUROSCIENCE
Referencias:
Año: 2006 vol. 6 p. 1539 - 1546
ISSN:
0953-816X
Resumen:
Abstract
Cerebral dysfunctions, including a high incidence of depression, are common findings in human type 1 diabetes mellitus. An
association between depression and defective hippocampal neurogenesis has been proposed and, in rodents, antidepressant
therapy restores neuronal proliferation in the dentate gyrus. Hippocampal neurogenesis is also deficient in diabetic mice, which led us
to study whether the selective serotonin reuptake inhibitor fluoxetine influences cell proliferation in streptozotocin-diabetic animals.
Diabetic and control C57BL ⁄ 6 mice received fluoxetine (10 mg ⁄ kg ⁄ day, i.p., 10 days) and dentate gyrus cell proliferation was
measured after a single injection of 5-bromo-2¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.⁄ 6 mice received fluoxetine (10 mg ⁄ kg ⁄ day, i.p., 10 days) and dentate gyrus cell proliferation was
measured after a single injection of 5-bromo-2¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.
Cerebral dysfunctions, including a high incidence of depression, are common findings in human type 1 diabetes mellitus. An
association between depression and defective hippocampal neurogenesis has been proposed and, in rodents, antidepressant
therapy restores neuronal proliferation in the dentate gyrus. Hippocampal neurogenesis is also deficient in diabetic mice, which led us
to study whether the selective serotonin reuptake inhibitor fluoxetine influences cell proliferation in streptozotocin-diabetic animals.
Diabetic and control C57BL ⁄ 6 mice received fluoxetine (10 mg ⁄ kg ⁄ day, i.p., 10 days) and dentate gyrus cell proliferation was
measured after a single injection of 5-bromo-2¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.⁄ 6 mice received fluoxetine (10 mg ⁄ kg ⁄ day, i.p., 10 days) and dentate gyrus cell proliferation was
measured after a single injection of 5-bromo-2¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.¢-deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine
treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells
was analysed by confocal microscopy after seven daily BrdU injections, using Tuj-1 ⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.⁄ b-III tubulin as a marker for immature neurones
and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj-1-BrdU-positive cells over total BrdU cells was 70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.70%.
In vehicle-treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values
without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In
addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with
controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity-related
hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes-associated depression
in humans.